There is still a paucity of hydrological data explaining the relationship between (rapid, millennial-scale) climate forcing and Mediterranean rainfall since the Last Glacial. We show that distinct lake-level fluctuations at Lake Trasimeno (Italy) are associated with changing aridity in the central Mediterranean during the last ˜47 800 years. The lake-level fluctuations are reconstructed based on carbonate mineral content and carbonate mineral species, as well as the stable oxygen and carbon isotope (δ18O and δ13C) geochemistry of endogenic carbonates. Low lake levels are linked to high carbonate, Mg-calcite and aragonite contents, and high δ18O and δ13C values. Inferred hydrological changes are linked to glacial–interglacial and, tentatively within the limitations of our chronology, to millennial-scale climate variability as well as the intensity of the Atlantic Meridional Overturning Circulation (AMOC). Prior to the Last Glacial Maximum (LGM), during intervals equivalent to Marine Isotope Stage 3 (MIS 3), a stronger AMOC associated with Greenland interstadial periods (Dansgaard/Oeschger (D/O) warm periods) and stronger Asian monsoon probably coincide with increased precipitation in central Italy as inferred from high lake levels at Lake Trasimeno. Periods of weak AMOC intensity such as during Greenland stadials (D/O cold periods), during Heinrich events, and weak Asian monsoons are correlated with lake level lowstands, which imply relatively dry conditions in central Italy. Lake Trasimeno’s water level during the LGM and the Lateglacial (MIS 2) is relatively stable, with recorded changes showing distinct similarities to orbital configurations. Although muted, high latitude climate forcing is still evident in the data during peak glacial conditions. The transition from D/O-like hydrological variability at Lake Trasimeno during MIS 3 to orbitally controlled fluctuations during the Lateglacial to Holocene transition coincides with an increasing amplitude in local winter and summer insolation, probably indicating increasing seasonality and a larger temperature gradient between low- and high-latitude settings.